Lipid peroxidation plays a pivotal role in the pathogenicity and maintenance of hepatitis. Thus, substances protecting hepatocyte membranes from lipid peroxidation are of great importance in the management of hepatotoxicity and hepatitis. The present work deals with the in vitro hepatoprotective activity of the methanol extract of Desmodium uncinatum, its sub-fractions, the major isolated compounds and some of their semi-synthetic derivatives in order to study structure activity relationships. Using hydrogen peroxide (H 2 O 2)-induced lipid peroxidation of hepatocyte membranes as a model, the hepatoprotective-guided phytochemical survey of the methanol extract of aerial parts of D. uncinatum was carried out by successive column chromatography. One of the most active compounds (Isovitexin) was chemically transformed to yield new semi-synthetic. The identification of isolated and semi-synthetic compounds was performed using NMR techniques, mass spectrometry and by comparison of their data with those reported in the literature. The n-butanol fraction was the most effective (IC 50 : 22.9 µg/mL) compared to the crude methanol extract (IC 50 : 43.6 µg/mL) and other fractions. The n-butanol sub-fractions FA (containing non-phenolic compounds) and FB (mainly containing phenolic compounds) exhibited respective IC 50 of 14.36 and 128.2 µg/ml.